The objectives of this project are to study the secretion of neurophysins in man, monkey and rat and to determine whether neurophysin secretion provides a measure of physiologic and pathophysiologic function of the posterior pitutitary. Individual neurophysins have now been isolated from human posterior pituitaries. Antisera raised in rabbits distinguished two specific antigenic sites on the isolated neurophysin peptides, and individual sensitive and specific radioimmunoassays for two human neurophysins have been developed. One assay measures a neurophysin which is specifically secreted in response to estrogen administration, Estrogen Stimulated Neurophysin (ESN). The other assay measures a neurophysin which is specifically secreted in response to cigarette smoking, Nicotine Stimulated Neurophysin (NSN). These two neurophysins are under independent physiologic control. ESN is specifically elevated in pregnancy and in cirrhosis (apparent estrogen effect). Both ESN and NSN are elevated in cord blood. ESN remains elevated in newborn plasma for 6 weeks while NSN falls significantly by 3 days. NSN is elevated during surgical stress and parturition, and diuretic induced volume depletion. Patients with IADH have elevated NSN and normal ESN. These tools will be used to investigate specific problems of posterior pituitary pathophysiology in the human: to investigate the function of the posterior pituitary in relation to cortisol insufficiency; and to study post-operative water retention in relation to neurohypophyseal function. Nicotine stimulation and NSN secretion will be used to investigate whether chlorpropamide has an action on the neurohypophysis. In addition, we will stimulate rabbits with rat neurophysin to develop specific rat neurophysin radioimmunoassays.